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2016 Grants - Almeida
Exploring Molecular Pathogenic Pathways Common to Alzheimer’s Disease and Frontotemporal Dementia
Sandra Almeida, Ph.D.
University of Massachusetts Medical School
2016 New Investigator Research Grant
How do variations in the CHMP2B gene increase the risk of developing dementia?
Frontotemporal dementia (FTD) is one of the most common types of dementia to affect people under the age of 65. An important focus of FTD research is to understand the genetic factors that may increase a person’s risk for developing the disease. Scientists believe there may be common genetic factors that promote both FTD and other dementias, such as Alzheimer’s disease.
A hallmark of Alzheimer’s disease is the accumulation of abnormal beta-amyloid protein fragments into potentially toxic “plaques” in the brain. Healthy brain cells can usually break down and remove abnormal or unused protein fragments before they accumulate. One gene, called CHMP2B (Charged Multivesicular Body Protein 2B) is important for the function of the cellular machinery that clears abnormal protein build-up in the brain. Variations in this gene have been associated with increased risk of FTD and Alzheimer’s disease, but the underlying biological changes are not yet clear.
Sandra Almeida, Ph.D. has developed an approach to study the impact of CHMP2B genetic variations on the molecular mechanisms common to both FTD and Alzheimer’s disease. Together with her colleagues, Dr. Almeida plans to genetically modify nerve cells in laboratory dishes by giving them the specific CHMP2B variations known to be associated with increased disease risk. She will measure the impact of these variations on the production of other molecules important for the break down and removal of abnormal proteins. In particular, she will examine how CHMP2B variations impact the accumulation of beta-amyloid and nerve cell health and function.
If successful, the results of this effort could help define how certain variations in the CHMP2B gene may contribute to the accumulation of potentially harmful proteins in brain during the development of a neurodegenerative disease. A better understanding of these mechanisms could lead to new therapeutics that target these processes to help slow or prevent the progression of multiple dementias, including FTD and Alzheimer’s disease.